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Publication : Acceleration of mammary neoplasia in aromatase transgenic mice by 7,12-dimethylbenz[a]anthracene.

First Author  Keshava N Year  2001
Journal  Cancer Lett Volume  167
Issue  2 Pages  125-33
PubMed ID  11369132 Mgi Jnum  J:69745
Mgi Id  MGI:2135387 Doi  10.1016/s0304-3835(01)00478-5
Citation  Keshava N, et al. (2001) Acceleration of mammary neoplasia in aromatase transgenic mice by 7,12-dimethylbenz. Cancer Lett 167(2):125-33
abstractText  Our studies using the aromatase transgenic mice model have shown that early exposure of mammary epithelium to in situ estrogen as a result of overexpression of aromatase predispose mammary tissue to preneoplastic changes. Here, we hypothesize that the preneoplastic changes induced by mammary estrogen in aromatase transgenic females may be susceptible to environmental carcinogens like 7,12-dimethylbenz[a]anthracene (DMBA), and may result in the acceleration and/or increase in the incidence of breast cancer. Results presented in this study show that tumors appeared in 25% of the mice that were treated with DMBA and all treated transgenic animals had microscopic evidence of neoplastic progression. Control non-transgenic females did not have significant changes even after treatment with DMBA. Consistent with increased neoplastic changes in DMBA-treated aromatase mice, we have seen an increase in the expression of genes involved in cell proliferation and cell cycle. We have also seen changes in the expression of oxidative stress markers and changes in estrogen-mediated growth factors. These studies indicate that more than one event is required for tumor formation, and that early estrogen exposure leading to preneoplastic changes in the mammary epithelial cells increases susceptibility to environmental carcinogens that may result in acceleration and/or an increase in the incidence of breast cancer.
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